The proposed research project aims at studying four biologically significant enzymes in prostaglandin metabolism. 15-Hydroxyprostaglandin dehydrogenase and prostaglandin A isomerase control the biological inactivation of prostaglandins, while prostaglandin E 9-keto reductase and prostaglandin E dehydrase regulate the interconversion of functionally different prostaglandins. These four enzymes will be isolated from respective sources of mammalian tissues. Affinity chromatography as well as conventional fractionation techniques will be employed to purify these enzymes. Physicochemical properties and kinetic mechanism of these enzymes will be studied. Regulation of these enzyme activities by various positive and negative modulators will be searched for and studies on the mode of action of these modulators will be carried out. The research program will provide an understanding of the basic properties of these enzymes, the nature and the mechanism of action of those factors involved in regulating the biological activity of prostaglandins. Moreover, it will give valuable information to the similar studies in various organs and further stimulate investigations on the roles of prostaglandins in various physiological systems. BIBLIOGRAPHIC REFERENCES: Tai, H.H. and Hollander, C.S. Regulation of prostaglandin metabolism: Activation of 15-hydroxyprostaglandin dehydrogenase by chlorpromazine and imipramine related drugs. Biochem. Biophys. Res. Commun. 68:814, 1976. Tai, H.H., Tai, C.L. and Hollander, C.S. Biosynthesis of prostaglandins in rabbit kidney medulla: Properties of prostaglandin synthase. Biochem. J. 154:257, 1976.